Airways smooth muscle will be studied in order to determine the mechanism by which repeated administration of histamine results in decreasing contractile response (tachyphylaxis). Tissue is mounted in isolated tissue baths and exposed to drugs while recording contractile responses. The tissue is frozen at various points in the contraction cycle using clamps cooled in liquid nitrogen and biochemical determinations are made on this tissue. Of primary interest is the cyclic nucleotide profile. Other biochemical methods include the measurement of prostaglandins in the effluent from superfused tissue. It is postulated that a defect in the mechanism which prevents over-constriction of the smooth muscle of the airways may participate in conditions of increased airway sensitivity. The long-term objective is to provide basic information on pulmonary smooth muslce function to determine the factors which control its responsiveness in health and disease.